rs959181

Variant names:

• chr15-84826346-A-G
• rs959181
• NM_020778.5:c.183-1138A>G

Your query was ambiguous. Multiple possible variants found:

• chr15-84826346-A-G
• chr15-84826346-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020778.5(ALPK3):​c.183-1138A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.844 in 152,170 control chromosomes in the GnomAD database, including 54,675 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.84 (54675 hom., cov: 31)
• Consequence: ALPK3 NM_020778.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.335
• Publications: 3 publications found

Genes affected

ALPK3 (HGNC:17574): (alpha kinase 3) Predicted to enable ATP binding activity; protein serine kinase activity; and protein serine/threonine kinase activity. Predicted to be involved in cardiac muscle cell development. Predicted to be active in nucleus. Implicated in hypertrophic cardiomyopathy. [provided by Alliance of Genome Resources, Apr 2022]

ALPK3 Gene-Disease associations (from GenCC):

• hypertrophic cardiomyopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• cardiomyopathy, familial hypertrophic 27

  Inheritance: AR, AD, SD Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.943 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALPK3	NM_020778.5	c.183-1138A>G		intron_variant	Intron 2 of 13	ENST00000258888.6	NP_065829.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALPK3	ENST00000258888.6	c.183-1138A>G		intron_variant	Intron 2 of 13	1	NM_020778.5	ENSP00000258888.6

Frequencies

GnomAD3 genomes AF: 0.844 AC: 128399 AN: 152050 Hom.: 54624 Cov.: 31

Gnomad AFR AF: 0.951

Gnomad AMI AF: 0.822

Gnomad AMR AF: 0.764

Gnomad ASJ AF: 0.859

Gnomad EAS AF: 0.944

Gnomad SAS AF: 0.789

Gnomad FIN AF: 0.756

Gnomad MID AF: 0.817

Gnomad NFE AF: 0.808

Gnomad OTH AF: 0.830

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.844 AC: 128504 AN: 152170 Hom.: 54675 Cov.: 31 AF XY: 0.840 AC XY: 62500 AN XY: 74378

African (AFR) AF: 0.951 AC: 39517 AN: 41550

American (AMR) AF: 0.763 AC: 11657 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.859 AC: 2980 AN: 3470

East Asian (EAS) AF: 0.944 AC: 4877 AN: 5168

South Asian (SAS) AF: 0.790 AC: 3811 AN: 4824

European-Finnish (FIN) AF: 0.756 AC: 8002 AN: 10584

Middle Eastern (MID) AF: 0.829 AC: 242 AN: 292

European-Non Finnish (NFE) AF: 0.808 AC: 54926 AN: 67982

Other (OTH) AF: 0.826 AC: 1746 AN: 2114

Alfa AF: 0.835 Hom.: 6473

Bravo AF: 0.850

Asia WGS AF: 0.867 AC: 3016 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.2
DANN	Benign	0.51
PhyloP100		0.34
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs959181; hg19: chr15-85369577;